Preparation and In Vitro Characterization of Quercetin and Chlorhexidine-loaded PLGA Nanoparticles for Oral Biofilm-Associated Pathologies

Objectives: This study aimed to develop and evaluate a dual-drug-loaded PLGA nanoparticle system incorporating quercetin (QUE) and chlorhexidine (CHX) for localized, sustained delivery, with potential application in biofilm-associated pathologies. Materials and methods: Single- and dual-drug systems containing CHX and QUE at different concentrations (1.5%, 5%, and 15%) were successfully loaded into poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) with high encapsulation efficiency. Physicochemical characterization was performed using dynamic light scattering (DLS), zeta potential analysis, SEM-EDX, FTIR, and thermal analysis (DSC and TGA). Release kinetics of QUE- and CHX-loaded nanoparticles were evaluated in an artificial saliva environment, and the amounts of CHX and QUE released were quantified by high-performance liquid chromatography (HPLC). Antimicrobial activity was assessed against Staphylococcus aureus and Escherichia coli using the disc diffusion method. Results: The prepared nanoparticles displayed spherical morphology with sizes ranging from 54.08 to 356.1 nm and zeta potentials from − 2.11 to -12.46 mV, indicating colloidal stability. FTIR and thermal analysis confirmed molecular dispersion of drugs and polymer-drug interactions. QUE showed complete release within 168 h in the single-drug system, whereas co-loading with CHX extended QUE retention, with 20% remaining after 240 h. CHX release reached ∼80% in both formulations. CHX/QUE nanoparticles demonstrated superior antibacterial activity compared to QUE-only systems, effectively inhibiting both Gram-positive and Gram-negative bacteria. Conclusion: These compounds and formulations are designed for clinical applications due to their slow, controlled release of the dual-active PLGA NP system.